Identifed a molecule that promotes immune system activation against cancer

Researchers at the Cima Universidad de Navarra have identified a molecule that promotes the activation of the immune system to tackle cancer. The study, carried out in animal models, shows that CD3 aptamers stimulate the expansion of T lymphocytes in a specific way, and could therefore be used to improve adoptive cell therapies such as TILs.

Adoptive cell therapy in cancer involves transferring immune system cells to the patient that have been selected and enhanced in the laboratory to produce a more efficient ‘adoptive’ (non-natural) immune response against the tumour. An example of adoptive therapy is TILs. They are based on expanding natural tumour-reactive lymphocytes. The problem with this type of therapy lies in the limited expansion capacity of these TILs, so compounds that induce a high division capacity without preserving the antigenic specificity of the lymphocytes are often used.

"Aptamers (or structured nucleic acids) are molecules selected through a process of artificial evolution in the laboratory. Our work confirms that these aptamers allow us to expand lymphocytes while maintaining their anti-tumour specificity without the need to genetically modify them, as is the case with CAR-Ts", explains Dr. Fernando Pastor, principal investigator of Cima's Aptamers Group and director of the study.

Proof of concept for clinical application

This CD3 aptamers act as specialised molecules that bind to receptors on key cells of the immune system: T lymphocytes. "T lymphocytes are the guardians of our immune system and, in order to be activated and do their job in the fight against cancer, they need to receive precise signals. This is where these CD3 aptamers come in. They act like keys that fit perfectly into the T-cell receptor, triggering their activation and allowing them to recognise and eliminate tumour cells more efficiently", says Dr Pastor. The results have been published in the scientific journal Molecular Therapy-Nucleic Acids.

This work, funded by the European Union through the Horizon 2020 programmes, has been carried out as a proof of concept in mouse animal models. According to the Cima researcher, "the next step is to assess whether this type of therapeutic agent can also be used to reactivate and expand human TILs and thus apply them in adoptive therapies in patients".

Bibliographic reference:

•    Molecular Therapy-Nucleic Acids 2024 Apr 23;35(2):102198.  doi: 10.1016/j.omtn.2024.102198. eCollection 2024 Jun 11. "CD3 aptamers promote expansion and persistence of tumor-reactive T cells for adoptive T cell therapy in cancer"